biostudies-literatureNie HKey Research and Development Program of the Department of Science and Technology of Ningxia Hui Autonomous Regione47249https://www.ebi.ac.uk/biostudies/studies/S-EPMC12851650biostudies-literatureUnknown105(4)This study aimed to identify autophagy-related genes with a causal role in ischemic stroke (IS) risk using a multi-omics Mendelian randomization (MR) approach. We integrated summary-level data for blood-derived DNA methylation (mQTLs), expression (eQTLs), and protein (pQTLs) quantitative trait loci for 594 autophagy-related genes with large-scale IS genome-wide association studies for discovery (GCST006908) and validation (FinnGen). Summary-data-based MR (SMR) with colocalization analysis was performed, supplemented by brain eQTL analysis, protein-protein interaction networking, and drug prediction. The analysis identified 113 mQTLs, 38 eQTLs, and 9 pQTLs associated with IS risk, with colocalization supporting shared causal variants for a subset. Validation in FinnGen confirmed 13 mQTLs anMedicineAutophagic molecular network in IS pathogenesis: A multi-omics Mendelian randomization study.PMC128516502021BEG03074Hei YZhang MZhang LMa TXu XNie HfalseAutophagic molecular network in IS pathogenesis: A multi-omics Mendelian randomization study.This study aimed to identify autophagy-related genes with a causal role in ischemic stroke (IS) risk using a multi-omics Mendelian randomization (MR) approach. We integrated summary-level data for blood-derived DNA methylation (mQTLs), expression (eQTLs), and protein (pQTLs) quantitative trait loci for 594 autophagy-related genes with large-scale IS genome-wide association studies for discovery (GCST006908) and validation (FinnGen). Summary-data-based MR (SMR) with colocalization analysis was performed, supplemented by brain eQTL analysis, protein-protein interaction networking, and drug prediction. The analysis identified 113 mQTLs, 38 eQTLs, and 9 pQTLs associated with IS risk, with colocalization supporting shared causal variants for a subset. Validation in FinnGen confirmed 13 mQTLs an2026-01-01T00:00:00Z2026 Jan2026-06-12T10:17:06.074Z2026-06-12T03:12:16.952ZS-EPMC128516504157845610.1097/MD.0000000000047249